A versatile approach to flavones via a one-pot Pd(II)-catalyzed dehydrogenation/oxidative boron-Heck coupling sequence of chromanones

Article abstract of DOI:10.1039/c5ob01911g

A variety of flavones were expediently synthesized from readily accessible chromanones via a one-pot sequence involving Pd(ii)-catalyzed dehydrogenation and oxidative boron-Heck coupling with arylboronic acid pinacol esters. In particular, the use of arylboronic acid pinacol esters was found to significantly improve the yield of the reaction.

Full text of DOI:10.1039/c5ob01911g

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A versatile approach to flavones via one-pot Pd(II)-catalyzed
dehydrogenation/oxidative boron-Heck coupling sequence of
chromanones†
Received 00th January 20xx,
Accepted 00th January 20xx
Jun Lee,‡,a Jihyun Yu,‡,a Seung Hwan Son,a Jinyuk Heo,a Taelim Kim,b Ji-Young An,a Kyung-Soo Inn,a
DOI: 10.1039/x0xx00000x
Nam-Jung Kim*,a
www.rsc.org/
A variety of flavones were expediently synthesized from readily accessible chromanones via a one-pot sequence involving
Pd(II)-catalyzed dehydrogenation and oxidative boron-Heck coupling with arylboronic acid pinacol esters. Especially, the
use of arylboronic acid pinacol esters was found to significantly improve the yield of the reaction.
and less reactive than chromones. Particularly, the oxidation
process of chromanones has been used for concise conversion into
chromones.7
Introduction
Flavones, a class of widely occurring natural products and their
synthetic derivatives, have received enormous attention in the field
of medicinal chemistry1 due to their fascinating biological activities
such as anti-oxidant, anti-inflammatory, anti-cancer and estrogen-
related functions.2 As representative routes to the structures of
such privileged flavones, several synthetic methods, including
intramolecular condensation of (2-hydroxyphenyl)-1, 3 diketones
following the Baker-Venkataraman rearrangement, the oxidative
cyclization of 2-hydroxychalcone, the Allan-Robinson reaction, and
Pd(0)-catalyzed cyclization, have been conventionally used in recent
decades.3 These approaches have often been reported to possess
the disadvantages of requiring multiple steps, using limited
reagents or starting materials, operating under harsh reaction
conditions, or providing low to moderate yields. Recently, a few
reports on the preparation of flavones from chromone using Pd(II)-
catalyzed C-H functionalization have been disclosed.4 Among them,
flavone synthesis via oxidative boron-Heck coupling5 is interesting
because it requires mild conditions, is conveniently available, uses a
moderate amount of reagents, and provides good to excellent
yields as well as regioselectivity.4a,4b This approach also showed
significant feasibility of late stage functionalization to provide
various substituted flavones. However, the preparation of various
chromones, the starting materials of the reaction, might be
sometimes difficult, partly due to their reactive α, β-unsaturated
carbonyl and enol ether moieties. In these cases, the chromones
have been occasionally synthesized and functionalized via other
intermediates such as chromanones, which are readily available6
In an effort to develop a more versatile approach to diverse
flavones, we considered it worthwhile to explore an approach to
flavone scaffolds using a Pd(II)-catalyzed reaction, directly from
chromanones instead of chromones. In 2011, Stahl and his
coworkers reported that Pd(II)-catalyzed dehydrogenation provided
efficient transformation of simple ketones to enones.8 In addition, a
recent work about direct transformation of chromanones into
flavones using simple arenes, reported by Hong and his coworkers,
have shown the feasibility of one-pot Pd(II) catalysis.4d Considering
Considering these previous reports that show the potential of Pd(II)
species to proceed through further Pd(II)-catalysis oxidative boron-
Heck coupling over dehydrogenation of the ketone, we envisaged
that the chromanones could be assembled into the flavones via
chromones generated in situ dehydrogenation and oxidative boron-
Heck coupling in a one-pot Pd(II)-catalysis sequence. Herein, we
report a one-pot Pd(II)-catalyzed dehydrogenation/oxidative boron-
Heck coupling sequence of chromanones as a concise and versatile
approach to the synthesis of flavones. (Scheme 1)
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In addition, most of the ligands used for boron-Heck reaction4a,5a-k
Scheme 1 One pot synthetic strategy toward flavones in this study
,
such as phenanthroline, were already known to be ineffective for
dehydrogenation in AcOH solvent.8a Therefore, we tried to optimize
the reaction condition conditions using DMSO, another suitable
solvent for the dehydrogenation process.8a In the presence of most
of the ligands reported to improve the boron-Heck reaction5a-k, low
to moderate yields of the flavone were obtained (entry 2-7). Among
them, the catalytic system including 5-nitro-1, 10 phenanthroline
(5-nitro phen) as a ligand afforded flavone 4a in 42% yield, along
with flavanone 5a, the conjugate addition product in 25% yield,
indicating that it was better than the other ligands under
incorporating conditions (entry 7).
In view of recent reports4b,5d,5k in which the conjugate addition
product can be obtained in a higher amount as the acidity of an
additive in the reaction increased, we supposed that the relatively
acidic property nature of phenylboronic acid 2a might increase the
amount of flavanone 5a, leading to decreased yield of the desired
flavone 4a. With this insight, we introduced phenylboronic acid
pinacol ester 2b, as a readily available and aprotic surrogate of
phenylboronic acid 2a to improve the reaction. To our delight, the
use of 2b in DMSO at 100 °C enables the reaction to exclusively
provide flavone 4a with the highest yield of 93% yield and
flavanone 3a in 1% yield. (entry 8).
Result and Discussion
To investigate the feasibility of the Pd(II)-catalyzed
dehydrogenation/oxidative boron-Heck coupling sequence for the
synthesis of flavones, chromanone 1a and phenylboronic acid 2a
were selected as the model compounds to screen and optimize the
reaction conditions (Table 1). Based on the speculation that the
dehydrogenation process might be a plausible starting point for the
sequence, we initially tested the reaction condition with Pd(TFA)2
catalyst, DMSO ligand and AcOH solvent under O2 atmosphere,
which are known to be optimal for Pd(II)-catalyzed
dehydrogenation.8 Use of this conditionthese reaction conditions
resulted in the formation of the desired flavone 4a, with 13% yield,
and chromone 3a as a the major product (34% yield, entry 1). This
result indicated that chromanone could be dehydrogenated, but
the resulting chromone might be poorly converted into the flavone
under the conditionthese reaction conditions.
Formatted: Indent: First line: 0.5 ch
Table 1. Optimization of the reaction conditions for one-pot
dehydrogenation/oxidative boron-Heck couplinga
Next, we focused on an additional investigation regarding the
solvent, the amount of the reagent and another Pd(II) catalystthe
attention was focused in investigating the solvent, the amount of
reagent and alternative Pd(II) catalysis. In the case of using DMF as
a solvent, flavone was successfully formed with 70% yield. However,
the use of other solvents, another alternative catalyst such as
Pd(OAc)2 and 1.5 equivalent of 2b resulted in a lower yield of the
desired productlower yields of the desired product. than yield
under the optimized condition using 1a (1.0 equiv.), 2b (3.0 equiv.),
Pd(TFA)2 (15 mol %), 5-nitro phen (30 mol %), and DMSO (1 mL)
under an O2 atmosphereHence, the optimized condition using 1a
(1.0 equiv.), 2b (3.0 equiv.), Pd(TFA)2 (15 mol%), 5-nitro phen (30
mol%), and DMSO (1 mL) under an O2 atmosphere, were used.
Yield (%)b
2a or
Entry
Ligand
DMSO
Solvent
2b
2a
2a
2a
2a
2a
2a
2a
2b
2b
2b
2b
2b
2b
2b
2b
2b
3a
HOAcAcOH 34
4a (5a)
13 (9)
0
1
2
DMSO
DMSO
DMSO
DMSO
43
76
70
35
24
1
3
pyridine
DMAP
2
4
2
5
bipyridine
11 (11)
19 (9)
42 (25)
93 (1)
2 (3)
4 (13)
1 (1)
3 (3)
70
6
phenanthroline DMSO
7
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
5-nitro phen
DMSO
DMSO
toluene
CH3CN
dioxane
THF
8
0
Table 2. Dehydrogenation/oxidative boron Heck coupling of 1a with
various arylboronic acid pinacol estersa
9
57
52
51
72
0
10
11
12
13
14c
15d
16e
17f
DMF
DMSO
DMSO
DMSO
0
72
13
0
72 (1)
70 (1)
Formatted: Superscript
2b
5-nitro phen
DMSO
0
83 (1)
Formatted: Indent: First line: 0.5 ch, Space
After: 0 pt
aReaction conditions: 1a (0.34 mmol, 1.0 equiv.), 2a or 2b (1.02
mmol, 3.0 equiv.), Pd(TFA)2 (0.05 mmol, 15 mol %), ligand (0.10
mmol, 30 mol %), and solvent (1 mL)under O2 for 48 hours.
bIsolated yield. c1.5 equiv. 2b. d10 mol % Pd(TFA)2 and 20 mol % 5-
nitro phen. e15 mol % Pd(OAc)2. f1a (6.84 mmol, 1.0 equiv.), 2b
(20.53 mmol, 3.0 equiv.), Pd(TFA)2 (1.03 mmol, 15 mol%), 5-nitro
phen (2.05 mmol, 30 mol%), and DMSO (10 mL) under O2 for 48
hours.
2 | J. Name., 2012, 00, 1-3
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aReaction conditions: 1 (1.0 equiv.), 2b (3.0 equiv.), Pd(TFA)2 (15
mol %), 5-nitro phen (30 mol %), and DMSO under O2 for 48 hours.
To further explore the scope and limitations of this procedure, the
reaction with a series of chromanone 1 and phenylboronic acid
pinacol ester 2b was investigated under the given conditions. As
shown in table 3, most of the chromanones could be readily
transformed into the corresponding functionalized flavones in
moderate to good yields, with both weakly and strongly electron
withdrawing (4q-s) or donating substituents (4t-w) on the phenyl
group of the chromanone. H+-labile acetal group (4x) and OH--labile
ester functional group (4y) were tolerant in the reaction. More
importantly, dimethoxy chromanones and catechol-derived
arylboronic acid pinacol ester successfully underwent
dehydrogenation/oxidative boron Heck coupling to provide the
corresponding flavones (4m-n, and 4w-x, respectively), indicating
that this methodology could be extended to the synthesis of
biologically active functionalized flavones bearing primarily
dimethoxy or dihydroxyl groups.
aReaction conditions: 1a (1.0 equiv.), arylboronic acid pinacol
ester 2 (3.0 equiv.), Pd(TFA)2 (15 mol %), 5-nitro phen (30
mol %), and DMSO under O2 for 48 hours.
Using the optimized condition, we tested a variety of aryl boronic
acid pinacol esters
2 to investigate the functional group
compatibility of the reaction (Table 2). Notably, the reaction was
widely applicable to the synthesis of flavones from chromanone 1a
with various arylboronic acid pinacol esters bearing either electron-
donating groups such as methyl (4b), tert-butyl (4c), phenyl (4d),
naphthyl (4e), hydroxyl (4j), and methoxy (4k-n) or electron
withdrawing groups such as fluorine (4f), chlorine (4g) and bromine
(4h). OH--labile ester functional group (4p) were also tolerant in the
reaction. The desired products were obtained in high yields, along
with a small amount of flavanone as a side product. The highest
yield of 90% was obtained by incorporating a trimethylsilyl phenyl
group (4i). In the case of incorporating strongly electron
withdrawing trifluoromethyl groupgroup, such as trifluoromethyl
(4o), the reaction provided the desired flavone 4o with relatively
lower yield compared to others, along with chromone 3a as a the
major product (70%).4a
To further demonstrate the potential utility of the one-pot
dehydrogenation/oxidative boron-Heck coupling sequence for the
synthesis of flavones, we attempted to synthesize apigenin (8), and
luteolin (10)9, natural flavones with significant biological activities1,
from readily available chromanone 6 using the methodology. As
expected, each corresponding intermediate (7 and 9) for the
synthesis of apigenin (8) and luteolin (10) was expediently
synthesized in yields of 87% and 75%, respectively, via the one-pot
dehydrogenation/oxidative boron-Heck coupling sequence.
Formatted: Font: Bold
Table 3. Dehydrogenation/oxidative boron-Heck coupling of 2b with
various chromonesa
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a versatile approach to diverse
In summary, we developed
flavones from readily available chromanones and arylboronic acid
pinacol esters via a Pd(II)-catalyzed dehydrogenation and oxidative
boron-Heck coupling reaction in a one-pot sequence. This approach
has the advantages of convenience, including easily accessible
reagents or starting materials and efficiency, providing high yields.
This methodology also provides
a facile route to biologically
interesting flavones including natural products such as apigenin and
luteolin. Additional investigations on broadening the scope of the
reaction to afford other related compounds and to perform
biological studies using the compounds are currently ongoing.
Scheme 2 Application of dehydrogenation/oxidative boron-Heck
coupling to the synthesis of natural flavones10
Experimental
General consideration
A
proposed mechanism of the sequential dehydrogenation/
Unless noted otherwise, all starting materials and reagents were
obtained from commercial suppliers (Aldrich, Alfa Aesar, and TCI)
and were used without further purification. Tetrahydrofuran and
Et2O were distilled from sodium benzophenone ketyl.
Dichloromethane, trimethylamine, acetonitrile and pyridine were
freshly distilled from calcium hydride. All solvents used for routine
isolation of products and chromatography were reagent grade and
glass distilled. Reaction flasks were dried at 100 °C. Air and moisture
sensitive reactions were performed under argon atmosphere. Flash
column chromatography was performed using silica gel 60 (230-400
mesh) with the indicated solvents. Thin-layer chromatography was
performed using 0.25 mm silica gel plates. Optical rotations were
measured using 100 nm cell of 1~2 mL capacity. 1H-NMR spectra
were recorded and obtained using on a Bruker 400 (400 MHz for 1H-
NMR) and Varian VNMR S500 (; 125 MHz for 13C-NMR)
spectrometer, respectively. 1H and 13C NMR chemical shifts are
reported in parts per million (ppm) relative to TMS
(tetramethylsilane), with the residual solvent peak used as an
internal reference. Signals are reported as m (multiplet), s (singlet),
d (doublet), t (triplet), q (quartet), bs (broad singlet), bd (broad
doublet), dd (doublet of doublets), dt (doublet of triplets), or dq
(doublet of quartets); the coupling constants are reported in hertz
(Hz). Mass spectra were obtained with VG Trio-2 GC-MS instrument.
High resolution mass spectra were obtained with JEOL JMS-AX
505WA instrument.
oxidative boron-Heck coupling is depicted in scheme 3. First, the
formation of a Pd(II) enolate might followmight be followed by β-
hydride elimination11 to generate the enone product 3a
(dehydrogenation), which could be
a starting material for the
oxidative boron-Heck coupling. Next, the arylboronic acid pinacol
ester would be transmetalated to form palladated aryl intermediate
B, which inserts into the electrophilic alkene of 3a, resulting in
Pd/alkyl intermediate C. Then, this intermediate is converted into
the desired coupled product 4a by the subsequent β-hydride
elimination (oxidative boron-Heck coupling). In an excess protic
environment, flavanone 5a might be produced through protonolysis
of intermediate C. During both of the reactions, Pd(0) species
formed in the reaction would be recycled into Pd(II) via [O] process,
where O2 plays a crucial role in the re-oxidation process of the
catalyst.
[O] Process
H2O2
(1/2 O2 + H2O)
OH
O
O
O
PdIIX2
2HX
1a
PdX
O
Pd0
O
O
O
O
O
PdII
X
O2
H
OR
B
A
Pd0
-H elimination
O
OR
General procedure for the synthesis of flavones. To a solution of
Pd(TFA)2 (0.05 mmol), and 5-nitro-1,10-phenanthroline (0.10 mmol)
in anhydrous DMSO (1mL) were added chromanone (0.34 mmol)
and phenyl boronic acid pinacol ester (1.02 mmol) under O2
atmosphere. The reaction mixture was stirred at 100 oC until
complete consumption of the starting material on TLC. Then, the
reaction mixture was diluted with EtOAc and filtered through a pad
of celite. The filtrate was concentrated in vacuo and purified by
column chromatography on silica gel (EtOAc/Hexanes).
PdII
X
PdII
X
2a or 2b
H
HX
O
Dehydrogenation
B
3a
O
O
PdII
X
protonolysis
if R = H (2a)
[O] Process
H
O
O
C
5a
-H elimination
O
H
PdII
X
2-phenyl-4H-chromen-4-one (4a). Prepared from 4-chromanone
and phenylboronic acid pinacol ester using the general procedure
described above. The residue was purified by silica gel column
chromatography (EtOAc : n-Hexane = 1 : 2) to afford 69 mg (93%) of
compound 4a. as a white solid; mp 96-97oC; 1H-NMR (CDCl3, 400
MHz) δ 8.22 (dd, 1H, J = 7.9, 1.5 Hz), 7.91-7.88 (m, 2H), 7.68 (m, 1H),
7.55-7.48 (m, 4H), 7.39 (m, 1H), 6.80 (s, 1H); 13C-NMR (CDCl3, 125
MHz) δ 178.6, 163.6, 156.5, 134.0, 132.0, 131.8, 129.3, 129.3, 126.5,
Oxidative
boron-Heck Coupling
O
4a
Scheme 3 Proposed mechanism of the reaction
Conclusion
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126.5, 125.9, 125.5, 124.2, 118.3, 107.8; LR-MS (FAB) m/z 223 134.1, 128.8, 128.7, 128.2, 128.2, 125.9, 125.6, 124.1, 118.2, 116.6,
(M+H+); HR-MS (FAB) calcd for C15H10O2 (M+H+) 223.0759; found 116.4, 107.6.
223.0762.
2-(4-chlorophenyl)-4H-chromen-4-one (4g). Prepared from 4-
2-(p-tolyl)-4H-chromen-4-one (4b). Prepared from 4-chromanone chromanone and 4-chlorophenylboronic acid pinacol ester using the
and 4-tolylboronic acid pinacol ester using the general procedure general procedure described above. The residue was purified by
described above. The residue was purified by silica gel column silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
chromatography (EtOAc : n-Hexane = 1 : 2) to afford 60 mg (75%) of afford 52 mg (60%) of compound 4g as a yellow solid; mp 188-190
compound 4b as a pale yellow solid; mp 111-113 oC; 1H-NMR (CDCl3, oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.22 (d, 1H, J = 7.9 Hz), 7.86 (d, 2H, J
400 MHz) δ 8.22 (d, 1H, J = 7.9Hz), 7.82 (d, 2H, J = 8.2Hz), 7.69 (t, 1H, = 7.6 Hz), 7.71 (m, 1H), 7.56 (d, 1H, J = 8.4 Hz), 7.50 (d, 2H, J = 7.6
J = 8.2Hz), 7.56 (d, 1H, J = 8.4Hz), 7.41 (t, 1H, J = 7.5Hz), 7.32 (d, 1H, Hz), 7.43 (t, 1H, J = 7.6 Hz), 6.79 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ
J = 8.0Hz), 6.80 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 178.7, 163.8, 178.5, 162.4, 156.4, 138.1, 134.1, 130.5, 129.6, 129.6, 127.8, 127.8,
156.5, 142.5, 133.9, 130.0, 130.0, 129.2, 126.5, 126.5, 125.9, 125.4, 126.0, 125.6, 124.1, 118.3, 107.9; LR-MS (FAB) m/z 257 (M+H+); HR-
Formatted: Font: Not Bold, Font color: Auto
124.2, 118.3, 107.2, 21.8.
MS (FAB) calcd for C15H9ClO2 (M+H+) 257.0369; found 257.0372.
Formatted: Font: Not Bold
2-(4-(tert-butyl)phenyl)-4H-chromen-4-one (4c). Prepared from 4-
2-(4-bromophenyl)-4H-chromen-4-one (4h). Prepared from 4-
chromanone and 4-t-butylphenylboronic acid pinacol ester using chromanone and 4-bromo phenylboronic acid pinacol ester using
the general procedure described above. The residue was purified by the general procedure described above. The residue was purified by
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
afford 76 mg (81%) of compound 4c as a pale yellow solid; mp 97- afford 49 mg (48%) of compound 4h as a pale yellow solid; mp 164-
99 oC; 1H-NMR (CDCl3, 400 MHz) δ 8.23 (dd, 1H, J = 7.9, 1.6 Hz), 7.86 166 oC; 1H-NMR (CDCl3, 400 MHz) δ 8.22 (d, 1H, J = 7.9 Hz), 7.79 (d,
(d, 2H, J = 6.8 Hz), 7.68 (td, 1H, J = 7.3, 1.6 Hz), 7.57-7.53 (m, 3H), 2H, J = 8.4Hz), 7.74-7.63 (m, 3H), 7.56 (d, 1H, J = 8.4Hz), 7.43 (t, 1H,
7.40 (t, 1H, J = 7.5 Hz), 6.81 (s, 1H), 1.37 (s, 9H); 13C-NMR (CDCl3, J = 7.5Hz), 6.80 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 178.5, 162.5,
125 MHz) δ 178.7, 163.8, 156.5, 155.6, 133.9, 129.2, 126.4, 126.4, 156.4, 134.2, 132.6, 132.6, 131.0, 127.9, 127.9, 126.6, 126.0, 125.6,
126.3, 126.3, 125.9, 125.4, 124.2, 118.3, 107.3, 35.3, 31.4, 31.4, 124.2, 118.3, 107.9.
31.4; LR-MS (FAB) m/z 279 (M+H+); HR-MS (FAB) calcd for C19H18O2
(M+H+) 279.1385; found 279.1380.
2-(4-(trimethylsilyl)phenyl)-4H-chromen-4-one (4i). Prepared
from 4-chromanone and 4-(Trimethylsilyl) phenylboronic acid
2-([1,1'-biphenyl]-4-yl)-4H-chromen-4-one (4d). Prepared from 4- pinacol ester using the general procedure described above. The
chromanone and 4-biphenylboronic acid pinacol ester using the residue was purified by silica gel column chromatography (EtOAc :
general procedure described above. The residue was purified by n-Hexane = 1 : 2) to afford 89 mg (90%) of compound 4i4b as a pale
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to yellow solid; mp 78-80 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.22 (dd, 1H,
afford 75 mg (75%) of compound 4d as a pale yellow solid; mp 142- J = 8.0 Hz, J=1.5 Hz), 7.87 (d, 2H, J = 8.2 Hz), 7.72-7.63 (m, 3H), 7.56
144 oC; 1H-NMR (CDCl3, 400 MHz) δ 8.23 (d, 1H, J = 7.9 Hz), 7.98 (d, (d, 1H, J = 8.5 Hz), 7.40 (t, 1H, J = 7.4 Hz), 6.84 (s, 1H); 13C-NMR
2H, J = 8.2 Hz), 7.74-7.63 (m, 5H), 7.57 (d, 1H, J = 8.4 Hz), 7.48 (t, 2H, (CDCl3, 125 MHz) δ 178.8, 163.7, 156.6, 145.7, 134.2, 134.0, 132.2,
J = 7.4 Hz), 7.43-7.38 (m, 2H), 6.86 (s, 1H); 13C-NMR (CDCl3, 125 MHz) 126.0, 125.6, 125.5, 124.3, 118.4, 107.9, -1.1.
δ 178.6, 163.3, 156.5, 144.6, 140.0, 134.0, 130.7, 129.3, 129.3,
2-(3-hydroxyphenyl)-4H-chromen-4-one (4j). Prepared from 4-
128.5, 127.9, 127.9, 127.4, 127.4, 127.0, 127.0, 126.0, 125.5, 124.3, chromanone and 3-hydroxyphenylboronic acid pinacol ester using
118.3, 107.7; LR-MS (FAB) m/z 299 (M+H+); HR-MS (FAB) calcd for the general procedure described above. The residue was purified by
C
21H14O2 (M+H+) 299.1072; found 299.1067.
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
2-(naphthalen-2-yl)-4H-chromen-4-one (4e). Prepared from 4- afford 55 mg (69%) of compound 4j as a white solid; mp 210 oC;. 1H-
chromanone and naphthalene-2-boronic acid pinacol ester using NMR (DMSO-d6, 400 MHz) δ 9.93 (s, 1H), 8.07 (d, 1H, J = 7.8 Hz),
the general procedure described above. The residue was purified by 7.85 (m, 1H), 7.78 (m, 1H), 7.55-7.50 (m, 2H), 7.46 (m, 1H), 7.39 (t,
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to 1H, J = 7.9 Hz), 7.02 (d, 1H, J = 8.1 Hz), 6.95 (s, 1H); 13C-NMR (DMSO-
afford 80 mg (87%) of compound 4e4b as a pale yellow solid; mp d6, 125 MHz) δ 177.8, 163.4, 158.6, 156.4, 135.0, 133.1, 131.0,
148-150 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.45 (s, 1H), 8.24 (dd, 1H, J 126.2, 125.5, 124.1, 119.6, 119.2, 117.9, 113.5, 107.6; LR-MS (FAB)
= 7.9 Hz, J=1.2 Hz), 8.00-7.83 (m, 4H), 7.71 (td, 1H, J = 7.8 Hz, J=1.4 m/z 239 (M+H+); HR-MS (FAB) calcd for C15H10O3 (M+H+) 239.0708;
Hz), 7.61 (d, 1H, J = 8.3Hz), 7.60-7.52 (m, 2H), 7.42 (t, 1H, J = 7.5 Hz), found 239.0707.
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6.94 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 178.7, 163.6, 156.6, 134.9,
134.1, 133.1, 129.3, 129.2, 129.1, 128.3, 128.1, 127.3, 127.2, 126.0, chromanone and 4-methoxyphenylboronic acid pinacol ester using
125.5, 124.3, 122.7, 118.4, 108.1. the general procedure described above. The residue was purified by
2-(4-methoxyphenyl)-4H-chromen-4-one (4k). Prepared from 4-
2-(4-fluorophenyl)-4H-chromen-4-one (4f). Prepared from 4- silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
chromanone and 4-fluorophenylboronic acid pinacol ester using the afford 62 mg (73%) of compound 4k as a white solid; mp 154-156
general procedure described above. The residue was purified by oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.21 (dd, 1H, J = 7.9, 1.6 Hz), 7.86 (d,
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to 2H, J = 8.8 Hz), 7.67 (t, 1H, J = 7.6 Hz), 7.53 (d, 1H, J = 8.2 Hz), 7.39 (t,
afford 57 mg (70%) of compound 4f3s as a yellow solid; mp 148-150 1H, J = 7.6 Hz), 7.00 (d, 2H, J = 8.8 Hz), 6.73 (s, 1H), 3.87 (s, 3H); 13C-
oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.21 (dd, 1H, J = 7.9 Hz, J=1.5 Hz), NMR (CDCl3, 125 MHz) δ 178.6, 163.6, 162.6, 156.4, 133.8, 128.2,
7.97-7.86 (m, 2H), 7.70 (td, 1H, J = 8.6 Hz, J=1.5 Hz), 7.55 (d, 1H, J = 128.2, 125.8, 125.3, 124.2, 124.1, 118.2, 114.7, 114.7, 106.4, 55.7;
8.4 Hz), 7.42 (t, 1H, J = 7.3 Hz), 7.20 (t, 2H, J = 8.6 Hz), 6.76 (s, 1H); LR-MS (FAB) m/z 253 (M+H+); HR-MS (FAB) calcd for C16H12O3 (M+H+)
13C-NMR (CDCl3, 125 MHz) δ 178.5, 166.0, 164.0, 162.6, 156.4, 253.0865; found 253.0863.
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2-(3-methoxyphenyl)-4H-chromen-4-one (4l). Prepared from 4- 156.5, 153.8, 134.2, 134.1, 130.5, 130.5, 129.7, 129.3, 128.9, 128.9,
chromanone and 3-methoxyphenylboronic acid pinacol ester using 128.0, 128.0, 126.0, 125.6, 124.2, 122.8, 122.8, 118.3, 107.9.
the general procedure described above. The residue was purified by
6-nitro-2-phenyl-4H-chromen-4-one (4q). Prepared from 6-
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to nitrochromanone and phenylboronic acid pinacol ester using the
afford 67 mg (79%) of compound 4l as a white solid; mp 125-128 oC;. general procedure described above. The residue was purified by
1H-NMR (CDCl3, 400 MHz) δ 8.22 (dd, 1H, J = 7.9, 1.6 Hz), 7.69 (td, silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
1H, J = 7.8, 1.7 Hz), 7.56 (d, 1H, J = 8.4 Hz), 7.49 (d, 1H, J = 7.9 Hz), afford 35 mg (51%) of compound 4q as a yellow solid; mp 184-187
7.44-7.40 (m, 3H), 7.06 (m, 1H), 6.81 (s, 1H), 3.88 (s, 3H); 13C-NMR oC;. 1H-NMR (CDCl3, 400 MHz) δ 9.10 (d, 1H, J = 2.8 Hz), 8.55 (dd, 1H,
(CDCl3, 125 MHz) δ 178.7, 163.4, 160.2, 156.5, 134.0, 133.3, 130.4, J = 9.2, 2.8 Hz), 7.95-7.93 (m, 2H), 7.75 (d, 1H, J = 9.2 Hz), 7.63-7.55
125.9, 125.5, 124.2, 118.9, 118.3, 117.4, 112.0, 108.0, 55.7; LR-MS (m, 3H), 6.90 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 177.0, 164.4,
(FAB) m/z 253 (M+H+); HR-MS (FAB) calcd for C16H12O3 (M+H+) 159.3, 145.1, 132.6, 131.0, 129.5, 129.5, 128.4, 126.7, 126.7, 124.3,
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253.0865; found 253.0864.
2-(3,4-dimethoxyphenyl)-4H-chromen-4-one (4m). Prepared from calcd for C15H9NO4 (M+H+) 268.0610; found 268.0607.
4-chromanone and 3,4-dimethoxyphenylboronic acid pinacol ester 6-fluoro-2-phenyl-4H-chromen-4-one (4r). Prepared from 6-
122.7, 120.1, 108.1; LR-MS (FAB) m/z 268 (M+H+); HR-MS (FAB)
using the general procedure described above. The residue was fluorochromanone and phenylboronic acid pinacol ester using the
purified by silica gel column chromatography (EtOAc : n-Hexane = 1 : general procedure described above. The residue was purified by
2) to afford 62 mg (65%) of compound 4m as a pink solid; mp 144- silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
146 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.21 (dd, 1H, J = 7.9, 1.6 Hz), afford 57 mg (79%) of compound 4r as a yellow solid; mp 123-127
7.68 (td, 1H, J = 7.8, 1.6 Hz), 7.56 (d, 2H, J = 8.4 Hz), 7.43-7.37 (m, oC;. 1H-NMR (CDCl3, 400 MHz) δ 7.91 (dd, 2H, J = 7.8, 1.5 Hz), 7.86
2H), 6.98 (d, 1H, J = 8.5 Hz), 6.75 (s, 1H), 3.98 (s, 3H), 3.96 (s, 3H); (dd, 1H, J = 8.2, 3.1 Hz), 7.59-7.50 (m, 4H), 7.42 (m, 1H), 6.81 (s, 1H);
13C-NMR (CDCl3, 125 MHz) δ 178.5, 163.6, 156.4, 152.3, 149.5, 13C-NMR (CDCl3, 125 MHz) δ 177.8, 163.9, 160.8, 158.9, 152.7,
133.8, 125.9, 125.3, 124.4, 124.1, 120.2, 118.2, 111.4, 109.0, 106.7, 132.0, 131.7, 129.3, 126.5, 125.4, 125.4, 122.2, 122.0, 120.4, 120.4,
56.3, 56.3; LR-MS (FAB) m/z 283 (M+H+); HR-MS (FAB) calcd for 111.0, 110.8, 107.1; LR-MS (FAB) m/z 241 (M+H+); HR-MS (FAB)
C17H14O4 (M+H+) 283.0970; found 283.0967.
calcd for C15H9FO2 (M+H+) 241.0665; found 241.0661.
2-(2,4-dimethoxyphenyl)-4H-chromen-4-one (4n). Prepared from
6-chloro-2-phenyl-4H-chromen-4-one (4s). Prepared from 6-
4-chromanone and 2,4-dimethoxyphenylboronic acid pinacol ester chlorochromanone and phenylboronic acid pinacol ester using the
using the general procedure described above. The residue was general procedure described above. The residue was purified by
purified by silica gel column chromatography (EtOAc : n-Hexane = 1 : silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
2) to afford 44 mg (46%) of compound 4n as a yellow solid; mp 127- afford 56 mg (80%) of compound 4s as a yellow solid; mp 178-180
129 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.22 (dd, 1H, J = 7.9, 1.6 Hz), oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.17 (d, 1H, J = 2.5 Hz), 7.91-7.88 (m,
7.90 (d, 1H, J = 8.8 Hz), 7.65 (td, 1H, J =7.9, 1.6 Hz), 7.50 (d, 1H, J = 2H), 7.63 (dd, 1H, J = 8.9, 2.6 Hz), 7.55-7.50 (m, 4H), 6.81 (s, 1H);
8.4 Hz), 7.38 (t, 1H, J = 7.2 Hz), 7.15 (s, 1H), 6.63 (dd, 1H, J = 2.3 Hz), 13C-NMR (CDCl3, 125 MHz) δ 177.4, 163.9, 154.8, 134.2, 132.1,
6.55 (d, 1H, J = 2.3 Hz), 3.92 (s, 3H), 3.88 (s, 3H); 13C-NMR (CDCl3, 131.6, 131.4, 129.4, 129.4, 126.6, 126.6, 125.4, 125.1, 120.1, 107.7;
125 MHz) δ 179.2, 163.5, 161.1, 159.9, 156.6, 133.6, 130.7, 125.8, LR-MS (FAB) m/z 257 (M+H+); HR-MS (FAB) calcd for C15H9ClO2
125.0, 124.0, 118.1, 113.8, 111.6, 105.5, 99.1, 55.9, 55.8; LR-MS (M+H+) 257.0369; found 257.0368.
(FAB) m/z 283 (M+H+); HR-MS (FAB) calcd for C17H14O4 (M+H+)
6-methoxy-2-phenyl-4H-chromen-4-one (4t4t). Prepared from 6-
283.0970; found 283.0967.
methoxychromanone and phenylboronic acid pinacol ester using
2-(4-(trifluoromethyl)phenyl)-4H-chromen-4-one (4o). Prepared the general procedure described above. The residue was purified by
from 4-chromanone and 4-(Trifluoromethyl)phenylboronic acid silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
pinacol ester using the general procedure described above. The afford 52 mg (73%) of compound 4t as a white solid; mp 165-167
residue was purified by silica gel column chromatography (EtOAc : oC;. 1H-NMR (CDCl3, 400 MHz) δ 7.90 (dd, 2H, J = 7.8, 2.8 Hz), 7.58 (d,
n-Hexane = 1 : 2) to afford 27 mg (27%) of compound 4o3w as a 1H, J = 3.1 Hz), 7.55-7.47 (m, 4H), 7.27 (dd, 1H, J = 9.1, 3.1 Hz), 6.81
brown solid;. 1H-NMR (CDCl3, 400 MHz) δ 8.25 (dd, 1H, J = 7.9 Hz, (s, 1H), 3.90 (s, 3H); 13C-NMR (CDCl3, 125 MHz) δ 178.5, 163.4, 157.2,
J=1.4 Hz), 8.05 (d, 2H, J = 8.2 Hz), 7.80 (d, 2H, J = 8.3 Hz), 7.74 (td, 151.3, 132.1, 131.7, 129.2, 129.2, 126.5, 126.5, 124.8, 124.0, 119.7,
1H, J = 7.8 Hz, J=1.7 Hz), 7.60 (d, 1H, J = 8.4 Hz), 7.46 (t, 1H, J = 7.5 107.0, 105.1, 56.1; LR-MS (FAB) m/z 253 (M+H+); HR-MS (FAB) calcd
Hz), 6.88 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 178.5, 161.9, 156.5, for C16H12O3 (M+H+) 253.0865; found 253.0865.
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135.5, 134.4, 133.5, 126.9, 126.4, 126.3, 126.3, 126.3, 126.1, 125.8,
124.2, 118.4, 109.0.
7-methoxy-2-phenyl-4H-chromen-4-one (4u). Prepared from 7-
methoxychromanone and phenylboronic acid pinacol ester using
4-(4-oxo-4H-chromen-2-yl)phenyl benzoate (4p). Prepared from the general procedure described above. The residue was purified by
4-chromanone and (4-(benzoyloxy)phenyl)boronic acid pinacol silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to
ester using the general procedure described above. The residue was afford 58 mg (82%) of compound 4u as a white solid; mp 105-106
purified by silica gel column chromatography (EtOAc : n-Hexane = 1 : oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.12 (d, 1H, J = 8.7 Hz), 7.91-7.87 (m,
2) to afford 63 mg (54%) of compound 4p as a pale yellow solid; mp 2H), 7.53-7.49 (m, 3H), 6.99-6.93 (m, 2H), 6.75 (s, 1H), 3.92 (s, 3H);
124-125 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.27-8.18 (m, 3H), 8.01 (d, 13C-NMR (CDCl3, 125 MHz) δ 178.1, 164.4, 163.2, 158.2, 132.1,
2H, J = 8.7Hz), 7.75-7.64 (m, 2H), 7.61-7.50 (m, 3H), 7.47-7.37 (m, 131.6, 129.2, 129.2, 127.3, 126.4, 126.4, 118.1, 114.7, 107.7, 100.6,
3H), 6.84 (s, 1H); 13C-NMR (CDCl3, 125 MHz) δ 178.6, 165.0, 162.8, 56.1; LR-MS (FAB) m/z 253 (M+H+); HR-MS (FAB) calcd for C16H12O3
(M+H+) 253.0865; found 253.0865.
6 | J. Name., 2012, 00, 1-3
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6-methyl-2-phenyl-4H-chromen-4-one (4v). Prepared from 6-
2-(3,4-dimethoxyphenyl)-5,7-dimethoxy-4H-chromen-4-one (9).
from 5,7-dimethoxychromanone and 3,4-
methylchromanone and phenylboronic acid pinacol ester using the Prepared
general procedure described above. The residue was purified by dimethoxyphenylboronic acid pinacol ester using the general
silica gel column chromatography (EtOAc : n-Hexane = 1 : 2) to procedure described above. The residue was purified by silica gel
afford 62 mg (85%) of compound 4v as a pale yellow solid; mp 112- column chromatography (EtOAc : n-Hexane = 1 : 2) to afford 62 mg
116 oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.00 (s, 1H), 7.90 (dd, 2H, J = (75%) of compound 914 1H-NMR (CDCl3, 400 MHz) δ 7.49 (dd, 1H, J
.
7.5, 1.7 Hz), 7.54-7.43 (m, 5H), 6.80 (s, 1H), 2.44 (s, 3H); 13C-NMR = 8.5, 2.1 Hz), 7.30 (d, 1H, J = 2.0 Hz), 6.95 (d, 1H, J = 8.6 Hz), 6.60 (s,
(CDCl3, 125 MHz) δ 178.8, 163.5, 154.8, 135.5, 135.3, 132.1, 131.8, 1H), 6.55 (d, 1H, J = 2.2 Hz), 6.36 (d, 1H, J = 2.2 Hz), 3.97 (s, 3H), 3.95
129.2, 129.2, 126.5, 126.5, 125.3, 123.8, 118.1, 107.6, 21.2; LR-MS (s, 6H), 3.92 (s, 3H); 13C-NMR (CDCl3, 125 MHz) δ 177.8, 164.2, 161.1,
(FAB) m/z 237 (M+H+); HR-MS (FAB) calcd for C16H12O2 (M+H+) 160.8, 160.0, 151.9, 149.4, 124.2, 119.7, 111.3, 109.4, 108.8, 108.1,
237.0916; found 237.0914.
96.3, 93.1, 56.6, 56.3, 56.3, 56.0; LR-MS (FAB) m/z 343 (M+H+); HR-
5,7-dimethoxy-2-phenyl-4H-chromen-4-one (4w). Prepared from MS (FAB) calcd for C19H18O6 (M+H+) 343.1182; found 343.1181.
5,7-dimethoxychromanone and phenylboronic acid pinacol ester
using the general procedure described above. The residue was
Acknowledgements
purified by silica gel column chromatography (EtOAc : n-Hexane = 1 :
2) to afford 43 mg (63%) of compound 4w as a white solid; mp 200-
203 oC;. 1H-NMR (CDCl3, 400 MHz) δ 7.88-7.83 (m, 2H), 7.52-7.45 (m,
This research was supported by the Basic Science Research Program
through the National Research Foundation of Korea (NRF), which
was funded by the Ministry of Science, ICT & Future Planning (NRF-
3H), 6.67 (s, 1H), 6.56 (d, 1H, J = 2.3 Hz), 6.36 (d, 1H, J = 2.3 Hz), 3.95
(s, 3H), 3.91 (s, 3H); 13C-NMR (CDCl3, 125 MHz) δ 177.8, 164.3, 161.2,
160.9, 160.2, 131.8, 131.4, 129.2, 129.2, 126.2, 126.2, 109.5, 109.3,
2013R1A1A1062292).
96.4, 93.1, 56.7, 56.0; LR-MS (FAB) m/z 283 (M+H+); HR-MS (FAB)
calcd for C17H14O4 (M+H+) 283.0970; found 283.0970.
6-phenyl-8H-[1,3]dioxolo[4,5-g]chromen-8-one (4x). Prepared
Notes and references
from 6,7-methylenedioxy-chromanone and phenylboronic acid
1.
M. Singh, M. Kaur and O. Silakari, Eur. J. Med. Chem.,
2014, 84, 206.
pinacol ester using the general procedure described above. The
residue was purified by silica gel column chromatography (EtOAc :
n-Hexane = 1 : 2) to afford 50 mg (72%) of compound 4x as a yellow
solid; mp 210-212 oC;. 1H-NMR (CDCl3, 400 MHz) δ 7.90-7.83 (m, 2H),
7.54-7.47 (m, 4H), 6.96 (s, 1H), 6.76 (s, 1H), 6.11 (s, 2H); 13C-NMR
(CDCl3, 125 MHz) δ 177.6, 163.0, 153.8, 153.0, 146.4, 132.0, 131.6,
129.2, 129.2, 126.3, 126.3, 119.2, 107.2, 102.7, 102.6, 98.3; LR-MS
(FAB) m/z 267 (M+H+); HR-MS (FAB) calcd for C16H10O4 (M+H+)
267.0657; found 267.0657.
2.
(a) B. Havsteen, Biochem. Pharmacol., 1983, 32, 1141; (b)
J. A. Manthey, K. Grohmann and N. Guthrie, Curr. Med.
Chem., 2001, 8, 135; (c) D. F. Birt, S. Hendrich and W.
Wang, Pharmacol. Ther., 2001, 90, 157; (d) M. Lopez-
Lazaro, Curr. Med. Chem. Anticancer Agents, 2002, 2, 691;
(e) H. P. Kim, K. H. Son, H. W. Chang and S. S. Kang, J.
Pharmacol. Sci., 2004, 96, 229; (f) S. Chirumbolo, Inflamm.
Allergy Drug Targets, 2010, 9, 263; (g) C. Spatafora and C.
Tringali, Anticancer agents Med. Chem., 2012, 12, 902; (h)
Kumazawa, H. Takimoto, T. Matsumoto and K. Kawaguchi,
Curr. Parm. Des., 2014, 20, 857.
(a) V. N. Kalinin, M. V. Shostakovsky and A. B.
Ponomaryov, Tetrahedron Lett., 1990, 31, 4073; (b) M.
Cushman and D. Nagarathnam, Tetrahedron Lett., 1990,
31, 6497; (c) L. W. Mcgarry and M. R. Detty, J. Org. Chem.,
1990, 55, 4349; (d) P. G. Ciattini, E. Morera, G. Ortar and S.
S. Rossi, Tetrahedron, 1991, 47, 6449; (e) D. C. G. A. Pinto,
A. M. S. Silva and J. A. S. Cavaleiro, Tetrahedron Lett.,
1994, 35, 9459; (f) D. G. Powers, D. S. Casebier, D. Fokas,
W. J. Ryan, J. R. Troth and D. L. Coffen, Tetrahedron, 1998,
54, 4085; (g) D. E. Zembower and H. P. Zhang, J. Org.
Chem., 1998, 63, 9300; (h) H. Miao and Z. Yang, Org. Lett.,
2000, 2, 1765-1768; (i) P. Kumar and M. S. Bodas, Org.
Lett., 2000, 2, 3821; (j) J. A. Seijas, M. P. Vazquez-Tato and
R. Carballido-Reboredo, J. Org. Chem., 2005, 70, 2855; (k)
B. Liang, M. W. Huang, Z. J. You, Z. C. Xiong, K. Lu, R. Fathi,
J. H. Chen and Z. Yang, J. Org. Chem., 2005, 70, 6097; (l) A.
K. Ganguly, S. Kaur, P. K. Mahata, D. Biswas, B. N.
Pramanik and T. M. Chan, Tetrahedron Lett., 2005, 46,
4119; (m) E. Fillion, A. M. Dumas, B. A. Kuropatwa, N. R.
Malhotra and T. C. Sitler, J. Org. Chem., 2006, 71, 409; (n)
B. Kosmrlj and B. Sket, Org. Lett., 2007, 9, 3993; (o) K. H.
Kumar and P. T. Perumal, Tetrahedron, 2007, 63, 9531; (p)
E. Awuah and A. Capretta, Org. Lett., 2009, 11, 3210; (q)
4-oxo-2-phenyl-4H-chromen-7-yl pivalate (4y). Prepared from 4-
oxochroman-7-yl pivalate and phenylboronic acid pinacol ester
using the general procedure described above. The residue was
purified by silica gel column chromatography (EtOAc : n-Hexane = 1 :
2) to afford 34 mg (51%) of compound 4y12 as a pale yellow solid;
mp 129-132oC;. 1H-NMR (CDCl3, 400 MHz) δ 8.25 (d, 1H, J=8.7 Hz),
7.90 (dd, 2H, J=7.5 Hz, J=1.6 Hz), 7.56-7.47 (m, 3H), 7.39 (d, 1H,
J=2.1 Hz), 7.14 (dd, 1H, J=8.7 Hz, J=2.1 Hz), 6.82 (s, 1H), 1.40 (s, 9H);
13C-NMR (CDCl3, 125 MHz) δ 178.0, 176.6, 163.9, 157.0, 155.4,
132.0, 131.8, 129.3, 127.3, 126.5, 121.8, 119.7, 111.3, 107.9, 39.6,
27.3.
3.
5,7-dimethoxy-2-(4-methoxyphenyl)-4H-chromen-4-one
Prepared from 5,7-dimethoxychromanone and
(7).
4-
methoxyphenylboronic acid pinacol ester using the general
procedure described above. The residue was purified by silica gel
column chromatography (EtOAc : n-Hexane = 1 : 2) to afford 65 mg
(87%) of compound 713 1H-NMR (CDCl3, 400 MHz) δ 7.80 (d, 2H, J =
.
8.9 Hz), 6.98 (d, 2H, J = 8.9 Hz), 6.58 (s, 1H), 6.54 (d, 1H, J = 2.3 Hz),
6.35 (d, 1H, J = 2.2 Hz), 3.94 (s, 3H), 3.90 (s, 3H), 3.87 (s, 3H); 13C-
NMR (CDCl3, 125 MHz) δ 177.9, 164.1, 162.3, 161.1, 160.9, 160.0,
127.8, 127.8, 124.0, 114.6, 114.6, 109.4, 107.8, 96.3, 93.0, 56.6,
56.0, 55.7; LR-MS (FAB) m/z 313 (M+H+); HR-MS (FAB) calcd for
C18H16O5 (M+H+) 313.1076; found 313.1073.
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ARTICLE
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